What is a Cholesterol Patient to Think?

January 15, 2008

I have very high cholesterol. I don’t even want to tell you how high. But I am also a bit of a statin-phobe. So when my doctor prescribed Vytorin, despite the extremely attractive direct-to-consumer advertising, I resisted. Vytorin is a combination of Zetia and Zocor, two anti-cholesterol agents that act in different ways to affect cholesterol levels. You’ve seen the commercials with food and people who look alike because both food and heredity play a factor in your cholesterol levels. Despite all that, the Vytorin sat on my shelf, unused, much to the frustration of my physician.

But now, this week, a study called ENHANCE has been released whereby it is shown that one of the drugs, Zetia, involved in the combination therapy Vytorin, while lowering cholesterol, does not lessen plaque and therefore is not effective in lowering heart attack risk. Dr. Steven Nissen, head of cardiology at the Cleveland Clinic state in a Forbes article that physicians should only prescribe Vytorin as a last resort. Forbes also reports that the study results were available last year, but that there was a delay in their release, which will also result in another Congressional investigation.

None of this is good for the image of the industry, it goes without saying. But for those of us with a bottle of Vytorin sitting on our medicine shelf, it raises further question about decisions when and how to take pharmaceutical products. When do we supplant our physician’s opinion and advice with our own?

The companies involved have a lot of work to do, and interestingly, as of today, there is no information that I found on the Vytorin Web site to talk about the ENHANCE issue nor could I find anything on the Web site for Zetia. Is lower cholesterol better, or is it better to lower your plaque?

There is more at stake here than one drug. For society at large, it is about how we get and perceive the information we are getting about treatments and how we react to it in the course of our own treatments that is most important. And for me – I can only say that I, for one, wonder what is a patient to think? And I feel very left on my own to figure it out.

My husband is on Vytorin and he is not going to stop taking it. Why? Because we’ve seen results. He was on Lipitor previously and while we saw a drop in his LDL it was not as significant as with Vytorin – an no he did not do anything different with his diet or exercise regimen. At the end of the day you need to figure out what is right for you based on your own results and not just some clinical trial.

Published on http://www.brainblogger.com:
A Failed Attempt to Improve Misperceived Greatness: The ENHANCE Trial
While it seems that sponsors of clinical trials usually end up with results that clearly favor their meds studied in their trial, there are rare exceptions, and Merck and Schering proved that with their disappointing ENHANCE Trial, which many have heard about through the media not long ago. The drugs studied were Vytorin, which was compared with Zocor.
Vytorin is a combination med for high cholesterol and contains Merck’s Zocor, which is now generic, and Schering’s Zetia, which works differently than Zocor, which is one of many statin drugs. Both Vytorin and Zetia are co-promoted by Merck and Schering. So, several years ago, an outcomes study was initiated to prove superiority of Vytorin over Zocor as monotherapy. The trial was named the ENHANCE trial, possibly because Zocor is generic now, and not a priority from a profit paradigm of its creator.
After several years passed, a disappointment arrived for the sponsors of this trial, which was first brought to the attention of Schering in March of 2007, yet the results existed since the spring of 2006, I believe upon information and belief.
The disappointment is that Vytorin lacked anticipated benefit or superiority over Zocor. Since about 1 million scripts were written for both Vytorin and Zetia every week in 2007, combined with what I believe was about 5 billion in revenue for these two drugs that year, this was a problem for the drug makers, meaning a fear of shareholder reaction. Perhaps for Schering in particular, it was more of a calamity, since over half of their profits and earnings were from these two drugs with Schering, I understand.
Being the responsible corporations both companies are, of course, alterations occurred after such events were discovered that fractured numerous rules and regulations with clinical trials, possibly in illegal and unethical tactics.
The trial sponsors delayed the release of the trial results for secrecy reasons, it has been speculated. Results from the trial existed, yet were not disclosed at the time of their discovery. After several months of possessing these trial results that were only known to the manufacturers, they created or implemented some atrocious tactics to improve the trial’s unimpressive results following the original results of this ENHANCE study. At the end of 2007, the companies changed the primary endpoint of the trial, which is what the results were measured upon during the entire course of the trial. Sort of like sorting cards to make a good hand not dealt to you. Anyway, since their deliberate concealment of these trial results was clearly wrong, to respond to those who asked where the results were actually as they had been anticipated for quite some time, and while such trial manipulation was occurring and results were being kept secret, Schering stated that continued data analysis from the trial results was the etiology for the delay.
With clinical trials, case report forms are used to record data from the trials, and are created in a manner where further analysis is not normally necessary, as such forms are quite clear and often not subject to interpretation as implied by the trial sponsors, one could conclude. So at the end of 2007, both Merck and Schering got the attention of relevant government officials who contacted both companies regarding this ENHANCE trial due to such suspicions on the facts known and presented, and an investigation began into the activities of both companies regarding this trial at that point.
This became a catalyst for the ENHANCE trial results to be finally released at the beginning of 2008, which caught the attention of major media organizations, as expected. In the spring of 2008, a very large cardiology meeting was held, where the audience was told, I understand, to stick with statins due to this trial’s lack of outcomes for Vytorin, when the ENHANCE trial was discussed at this meeting. Furthermore, it has been said that a cardiologist at this meeting also suggested that a moratorium should occur with the utilization of Vytorin by prescribers, since statins are much less expensive, and are highly regarded, as they have been available for a couple of decades, starting with Mevacor in the 1980s. Of course and as expected, Merck and Schering were not pleased, nor were they surprised at the review of Vytorin at this particular meeting. The following month after this cardiology meeting, Schering’s earnings dropped by 48 percent, as I recall. Also during much of this year, Schering in particular blamed the media for amplifying the situation regarding the ENHANCE trial.
Now, these cholesterol drugs promoted by Merck and Schering, Zetia and Vytorin, were aggressively marketed in a number of ways, including investing I believe about 200million dollars in 2007 for DTC ads for these products. To add to this, and soon after both meds were launched, reps from both companies made inferences to doctors about outcomes regarding plaque accumulation and how Vytorin was superior in that area, which, of course, this ENHANCE trial proved it is in fact not the case whatsoever. It did not matter, apparently, to both Merck and Schering that such claims were is entirely void of proof, which is not unique to any pharma rep, in my opinion. No remorse or regret from the makers of these drug makers, either, which did not shock many. Yet what is known now is that these companies, as stated by other researchers, performed junk science with their deliberate manipulation of this ENHANCE trial using such tactics. Also, last year, Zetia and Vytorin had about 20 percent of the cholesterol lowering market. It does not seem that there will be an increase of this percentage because of this scandal.
Possibly if they presented the truth, the future of these meds might be better than what is anticipated presently.
Worst of all regarding this ENHANCE trial scandal is the harm caused to both doctors and patients. The ENHANCE trial concerned and confused both of these participants in the health care system. Furthermore, it’s likely they were devastated by being so clearly misled by the marketing of both Merck and Schering regarding the false benefits of Vytorin they were led to believe by the companies that promoted them- the health care providers in particular.
This whole situation is another example of the progressively frequent discovery of corruption of the scientific method by placing profits over the well-being of patients, which harms the well being of patients. In addition, most were shocked by Merck behaving in such a way in particular because of what use to be their excellent reputation as an ethical pharmaceutical company. And this alone shows the progression and infiltration of such damaging ethical atrophy that desperately needs to be stopped and corrected for the sake of others. For the sake of everyone.
Don’t just say something. Have something to say- to the right people, with conviction and with others who share your views.
“Waste no more time arguing what a good man should be. Be one.” — Marcus Aurelius
Dan Abshear

About This Blog

Eye on FDA is published by Mark Senak of FleishmanHillard's Washington, D.C. office. The thoughts and ideas in this blog and postings are strictly my own and are not screened by my employer. Everything posted on this blog is my personal opinion and does not necessarily represent the views of FleishmanHillard or its clients.